Rotifer (Brachionus plicatilis)의 생존율에 미치는 tributyltin (TBT)과 triphenyltin (TPT)의 독성

전중균 ( Jeon Jung Gyun ),이미희 ( Lee Mi Hui ),이지선 ( Lee Ji Seon ),이경선 ( Lee Gyeong Seon ),심원준 ( Sim Won Jun ),신영범 ( Sin Yeong Beom ),이수형 ( Lee Su Hyeong ) 한국환경생물학회 2003 환경생물 : 환경생물학회지 Vol.21 No.2

유기주석화합물은 독성이 강하고 잔존력이 강하여 수계환경으로 유입되면 해양생태계에 오랫동안 영향을 미친다. 이들 화합물이 해양생물에 미치는 영향에 관해서는 어류나 패류 등의 산업적 가치가 큰 생물종을 대상으로 한 연구는 적지 않지만, 해양생태계에서 먹이사슬의 가장 하부에 위치하며 기초생산을 담당하는 플랑크톤류에 미치는 영향에 관해서는 잘 알려져 있지 않다. 따라서 본 연구에서는 TBT류의 TBTC, TBTO, TBTA, TBTB를 비롯하여 TPT류의 TPTC, TPTF, TPTH가 기수산 rotifer의 생존에 미치는 독성(96hr-LC_(50))을 조사ㆍ비교하였다. 그 결과, TBT류에서는 TBTA(1.1ppb)가 가장 강하였고 TBTC(2.0), TBTB(3.3), TBTO(5.6)의 순이었으며, TPT류에서는 TPTF(1.0), TPTC(1.1), TPTH(1.6)의 순이었다. 이 결과 TPT류가 전반적으로 TBT류에 비해 독성이 강하다는 것을 보여준다. This study was conducted to evaluate the effect of organotin compounds on rotifer (Brachionus plicatilis), which is important as food organism of aqua-cultured fish and shellfish. To evaluate the toxicities of tributyltin compounds such as tributyltin chloride (TBTC), tributyltin oxide (TBTO), tributyltin acetate (TBTA) and tributyltin benzoate (TBTB), and triphenyltin compounds such as triphenyltin chloride (TPTC), triphenyltin fluoride (TPTF), triphenyltin hydroxide (TPTH), the survival rates of rotifer exposed to these compounds were measured as the 96 hr-LC50. Exposed concentrations were from 0.5 to 8 bbp depending on compounds. Based on 96 hr-LC_(50) value, the order of toxicity in TBTs was TBTA (1.1 ppb) > TBTC (2.0) > TBTB (3.3) > TBTO (5.6), and that in TPTs was TPTF (1.0) 2TPTC (1.1) > TPTH (1.6). Triphenyltin compounds were slightly higher toxic than tributyltins. The toxicity is likely to depend on alkyl or aryl group other than halogen or the other substituted radicals.

Mechanisms of Tributyltin-induced Leyding Cell Apoptosis

Lee, Kyung Jin,Kim, Deok Song,Ra, Myung Suk,Wui, Seong Uk,Im, Wook Bin,Choi, Hueng Sik,Lee, Jong Bin 한국환경독성학회 2003 환경독성보건학회지 Vol.18 No.2

본 연구는 환경 호르몬으로 분류된 67종 중의 하나인, 선저 도료나 어망, 어구 및 방오페인트 재료로 사용되어지고 유기주석화합물(tributyltin)을 사용하여 설치류의 웅성생식세포에서 세포자연사를 일으키는 작용기작을 조사하였다. 먼저 흰쥐의 레이딕 세포주인 R2C에 유기주석화학물을 농도별 (1~500nM)로 처리한 후 DNA fragment현상을 전기영동법을 통하여 조사하였다. 그 결과 유기주석화합물을 처리한 군들에서 대조군에 비하여 세포자연사현상이 농도 의존적으로 증가하였다. 유기주석화합물이 세포 내 칼슘이온(Ca^(2+)) 및 유해 산소종(reactive oxygen species)에 미치는 영향을 조사해본 결과 유기주석화합물 처리시 세포 내 칼슘이온 및 유해 산소종이 시간에 의존적으로 크게 증가하였다. 또한 칼슘 킬레이터인 BAPTA를 전 처리한 경우 유기주석화합물에 의해 유도된 칼슘이온 및 유해 산소종이 대조군에 비해 유의성 있게 감소하였다. 이러한 세포자연사 과정이 미토콘드리아의 cytochrome c 방출에 의한 과정인지를 확인하기 위해 세포질 내 cytochrome c 양을 western blot법을 사용하여 확인해 본 결과 유기주석화합물 처리 시간 및 농도에 따라 증가하며, 이 또한 BAPTA를 전처리 한 경우 대조군에 비하여 유의성 있게 감소하였다. 또한 유기주석화합물이 세포자연사 유발 시 caspase-3 효소 활성과의 관계를 확인하기 위해 ELISA법을 사용하여 확인해 본 결과 유기주석화합물 처리 농도에 의존적으로 증가하였으며, caspase-3 효소 억제자로 잘 알려진 Z-DEVD FMK을 전 처리한 경우 유기주석화합물을 처리한 군에 비해 세포자연사율이 크게 감소하였다. 이러한 결과들을 종합해 볼 때 유기주석화합물은 세포 내 칼슘이온의 증가를 일으키고, 그로 인하여 세포질 내 유해산소종 및 cytochrome c의 양이 증가함으로써 세포자연사 다음 단계인 caspase 효소 활성의 증가를 통하여 흰쥐의 레이딕 세포주인 R2C의 세포자연사를 일으킬 것이라 추론할 수 있다. Tributyltin(TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. In this study, we investigated that the mechanisms underlying DNA fragmentation induced by TBT in the rat leydig cell line, R2C cells by fluorescence detector. TBT significantly induced intracellular Ca^2+ level in a time-de-pendent manner. The rise in intracellular Ca^2+ level was followed by a time=dependent generation of reactive oxygen species (ROS) at the cytosol level. Simultaneously, TBT induced the release of cytochrome c from the mitochondrial membrane into the cytosol. Furthermore, ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca^2+ chelator, indicating the important role of Ca^2+ in R2C during these early intracellular events. In addition, Z-DEVD FMK, a caspase-3 inhibitor, decreased apoptosis by TBT. Taken together, the present results indicated that the apoptotic pathway by TBT might start with an increase in intracellular Ca^2+ level, continues with release of ROS and cytochrome c from mitochondria, activation of caspases, and finally results in DNA fragmentation.

Tributyltin에 의한 흰쥐 정소 내 간질세포의 지방세포 유도와 세포자연사 증가

송연화,정지은,이현아,홍지희,양현원 한국발생생물학회 2010 발생과 생식 Vol.14 No.4

Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease testicular function by causing apoptosis in the testis, but this mechanism is not fully understood. Thus, in this study we examined whether TBT induces adipogenesis of the Leydig cells to find out the correlation between adipogenesis and apoptosis in the testis. Three week old SD male rats were orally administrated with sesame oil, 1 ㎎/㎏ of TBT, or 10 mg/㎏ of TBT daily for 1 week and weighed after administration. The testes obtained on day 8 were weighed and stained with BODIPY and TUNEL kit. Using total RNA extracted from the isolated Leydig cells, adipogenesis and apoptosis-related genes were analyzed by real-time PCR. The testicular weights of the rats treated with 10 ㎎/㎏ TBT were significantly decreased compared to those in the control rats treated with sesame oil. As a result of BODIPY staining, the number of Leydig cells stained with BODIPY was increased in the rats treated with 10 ㎎/㎏ TBT compared with the control rats. Similar to BODIPY staining results, the TUNEL assay showed that the apoptosis of Leydig cells was increased in TBT treated rats. The results of the gene expression analysis in the Leydig cells showed that the expression of adipogenesis-related genes (PPARγ, aP2, Perilipin, CD36) and apoptosis-related genes (TNFRSF1A, TNFSF10) was increased after TBT administration. The present study demonstrates that TBT induces the expression of adipogenesis-related and apoptosis-related genes in the Leydig cells leading to adipogenesis and apoptosis in the testes. These results suggest that the dysfunction of Leydig cells by TBT exposure may cause a loss in testicular function.

Tributyltin에 의한 흰쥐 흉선 내 상피세포의 지방세포 유도와 세포자연사 증가

양현원,이효진,이아라,안보람,전은제,정예지 한국발생생물학회 2011 발생과 생식 Vol.15 No.4

성 호르몬과 유사한 기능을 하는 것으로 알려진 내분비교란물질은 흰쥐 흉선세포에 세포자연사를 일으켜 흉선의기능을 감소시키는 것으로 보고되고 있으나, 그 작용 기전에 대해서는 잘 알려져 있지 않다. 따라서 본 연구에서는 내분비교란물질 중 하나인 Tributyltin(TBT)를 흰쥐에 투여한 후 흉선의 상피세포가 지방세포로 분화되는지를 조사하고, 이로인한 T 세포의 세포자연사와 연관성을 조사함으로써 TBT가 흉선기능에 미치는 영향을 알아보고자 하였다. 3주령 된 암컷 흰쥐에 각각 TBT 1, 10, 25 ㎎/㎏/day를 1주일 동안 경구 투여한 후, 흉선을 획득하여 무게와 세포 수를 측정하였고,파라핀 절편으로 H&E 염색, TUNEL 분석을 수행하였다. 또한 real-time PCR 방법으로 상피세포 표지 유전자들, 지방세포유도 유전자들과 세포자연사 관련 유전자들을 비교 분석하였으며, 유세포 분석기를 통해 세포자연사 정도를 조사하였다. 흉선의 무게와 세포 수는 대조군과 비교하여 TBT의 농도가 높을수록 유의하게 감소하였다. H&E 염색 결과, TBT의 농도가 증가할수록 흉선의 크기가 감소하고 피질과 수질의 경계가 흐려짐을 관찰하였다. TUNEL 염색 결과에서는 대조군에 비해 TBT를 투여한 군에서 세포자연사가 증가하였으며,유세포 분석결과에서도 TBT 농도 의존적으로 세포자연사가 증가하였다. Real-time PCR 결과, 상피세포 표지유전자인 EVA, IL-7, AIRE, KGF는 TBT의 농도가 증가 할수록 발현량이 유의하게 감소한 반면, 지방세포 유도와 관련된 유전자인 PPARγ, aP2, PEPCK, CD36은 TBT의 농도가증가할수록 발현량이 유의하게 증가하였다. 세포자연사와 관련된 유전자인 TNFα, TNFR1도 TBT의 농도가 증가할수록발현량이 유의하게 증가하였다. 위의 결과를 종합하여볼 때, 내분비교란물질인 TBT는 흉선 상피세포에 직접적으로 작용하여 지방세포로 분화 유도시킴으로써 흉선의 기능을 상실케 만들면서 T 세포의 발달에 영향을 미치는 것으로 보인다. 이러한 결과는 지속적으로 노출되는 TBT가 흉선의 기능을 떨어뜨림으로써 면역력 저하를 유발시킬 수 있음을 제시하고있다.

Effects of tributyltin on thymic epithelial cells and T lymphocytes in the mouse thymus

Jiye Kim(김지예),Eunhyea Park(박은혜),Hanbig Lee(이한빛),Ahhyun Lee(이아현),Philjae Kim(김필재),Sojeong Park(박소정),Eunji Im(임은지),Hyunwon Yang(양현원) 환경독성보건학회 2015 한국독성학회 심포지움 및 학술발표회 Vol.2015 No.10

Occurrence and bioaccumulation of persistent toxic substances in sediments and biota from intertidal zone of Abu Ali Island, Arabian Gulf

Yoon, Seo Joon,Hong, Seongjin,Kim, Taewoo,Lee, Junghyun,Kwon, Bong-Oh,Allam, Ahmed A.,Al-khedhairy, Abdulaziz A.,Khim, Jong Seong Elsevier 2019 MARINE POLLUTION BULLETIN Vol.144 No.-

<P><B>Abstract</B></P> <P>North Abu Ali Island is contaminated by crude oil from exogenous sources with a variety of persistent toxic substances (PTSs) being input into intertidal sediments. We detected an array of PTSs in sediments and benthic biota off north Abu Ali Island (Arabian Gulf), including 35 polycyclic aromatic hydrocarbons (PAHs), 6 alkylphenols (APEOs), 10 styrene oligomers (SOs), and tributyltin. The PTS concentrations were generally greater than those reported in other areas of Arabian Gulf. PAHs mainly originated from petrogenic sources, and APEOs and SOs seem to be of recent origin. Field-based biota-sediment accumulation factors (BSAF) varied by taxa and compounds, but clearly depended on the log K<SUB>ow</SUB> values of individual compounds. Some PTSs exceeded the established guidelines for sediments and biota; we found particularly great BSAFs for alkyl-naphthalenes (C1- and C2-), nonylphenol monoethoxylates, and <I>2,4,6-</I>triphenyl-<I>1</I>-hexene. Remediation will require on-site clean-up of toxic chemicals together with immediate efforts on preventing input of current pollution sources in the given area.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sediments and biota are moderately polluted by persistent toxic substances. </LI> <LI> Somewhat different compositions of PTSs occur between sediments and biota. </LI> <LI> Field-based BSAF values vary by taxa and PTSs based on log K<SUB>ow</SUB> of each compound. </LI> <LI> High BSAF values occur in alkyl-Na, NP1EOs, and few compounds of SOs. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Microarray-Mediated Transcriptome Analysis of the Tributyltin (TBT)- Resistant Bacterium Pseudomonas aeruginosa 25W in the Presence of TBT

Santosh K. Dubey,Tsutomu Tokashiki,Satoru Suzuk 한국미생물학회 2006 The journal of microbiology Vol.44 No.2

The tributyltin (TBT)-resistant bacterium, Pseudomonas aeruginosa 25W, which was isolated in seawater from the Arabian Sea, was subjected to transcriptome analysis in the presence of high concentrations of TBT. Only slight effects were observed at TBT concentration of 50 μM, but exposure to 500 μM resulted in the upregulation of 6 genes and the downregulation of 75. Among the 75 downregulated genes, 53% (40 out of 75) were of hypothetical function, followed by 14 transcriptional regulation- and translationassociated genes. The results of this study indicated that although the 25W strain was highly resistant to TBT, high concentrations of TBT result in toxic effect on the transcriptional and translational levels. The target genes likely belong to a specific category of transcription- and translation-associated genes rather than to other gene categories.

Bis(tributyltin) oxide가 랫드의 면역 및 성호르몬 활성에 미치는 영향

최한영,나규환 한국환경위생학회 1999 한국환경보건학회지 Vol.25 No.3

The purpose of this study finds out the effect of red ginseng extract(1.0g/kg) on bis(tributyltin)oxide(TBTO) (10, 20 and 40 mg/kg) which poisons against some organs like thyroid gland, liver, kidney, testis, ovary. Serum immunity and sex hormone activity of rats are examinned by gastric tubing for 3 weeks. 1he weights of each organ in treated group were increased, especially liver in females and those of testis in males were signignificantly increased at 10, 20 and 40 mg/kg(p<0.05, P<0.0l). In group treated with TBTO(10, 20 and 40 mg/kg) for females, the serum IgG level was significantly reduced in comparsion with control group(P<0.05). The group of females which were poisonned by TBTO and rGe was significantly recovered in TBTO 10 mg/kg + rGe 1.0 g/kg and TBTO 20 mg/kg + rGe 1.0 g/kg. In case of sex hormone activity of each sex, the estradiol activity of females and testosterone activity of males were sigoignificantly decreased rather than the control group. And control group by bis(tributyltio)oxide and red ginseng extract is just increased estiradiol activity.

연구보문 : 수질환경 ; 광양만에서 TBTCl (Tributyltin Chloride) 내성세균의 분리 및 분해활성

정성윤 ( Seong Yun Jeong ),손홍주 ( Hong Joo Son ),정남호 ( Nam Ho Jeoung ) 한국환경농학회 2011 한국환경농학회지 Vol.30 No.4

BACKGROUND: Tributyltin chloride is among the most toxic compounds known for aquatic ecosystems. Microorganisms are responsible for removal of TBTCl. Nevertheless, only limited number of marine bacteria were investigated for biodegradation of TBTCl in Korea. METHODS AND RESULTS: The number of TBTCl resistant bacteria ranged from 2.5 x 10(3) to 3.8 x 10(3) cfu/mL in the seawater, and ranged from 3.2 x 10(5) to 9.1 x 10(5) cfu/g in the surface sediment, respectively. The morphological, physiological, and biochemical characteristics of TBTCl resistant bacteria were investigated by API 20NE and other tests. The most abundant species of TBTCl resistant bacteria were Vibrio spp. (19.2%), Bacillus spp. (16.2%), Aeromonas spp. (15.2%), and Pseudomonas spp. (13.1%), etc. Eleven TBTCl resistant isolates also had a resistance to heavy metals (Cd, Cu, Hg, and Zn). Among them, isolate T7 showing the strong TBTCl-resistance was selected. This isolate was identified as the genus Pantoea by 16S rRNA gene sequencing and designated as Pantoea sp. T7. In addition, this bacterium was cultivated up to the growth of 50.7% after 60 hrs at TBTCl concentration of 500 μM. TBTCl-degrading activity of Pantoea sp. T7 was measured by GC-FPD analysis. As a result of biological TBTCl-degradation at TBTCl concentration of 100 μM, TBTCl-removal efficiency of Pantoeasp. T7 was 62.7%after 40 hrs. CONCLUSION(S): These results suggest that Pantoea sp. T7 is potentially useful for the bioremediation of TBT contamination.

Reponses of the Hepatic Microsomal Cytochrome P450 Monooxygenase System in Rock Bream Oplegnathus fasciatus Exposed to Tributyltin (TBT)

Hwang, Un-Gi,Lee, Jung-Sik,Kang, Ju-Chan The Korean Society of Fisheries and Aquatic Scienc 2013 Fisheries and Aquatic Sciences Vol.16 No.4

The study was conducted to investigate the responses of the hepatic microsomal cytochrome P450 monooxygenase system in the rock bream Oplegnathus fasciatus after chronic exposure to 0, 1, 2, 4, and $8{\mu}g/L$ tributyltin (TBT) concentrations for 4 weeks. Hepatic cytochrome 450 content and ethoxyresorufin O-deethylation (EROD) activity were found to significantly increase in fish treated with the higher concentration of TBT (${\geq}4{\mu}g/L$); however, no significant changes were observed in penthoxyresorufin O-deethylation (PROD) activity in all treated groups compared to the control group. These findings suggest that exposure to a low TBT concentration (${\geq}4{\mu}g/L$) has the potential to induce cytochrome 450 content and EROD enzyme activity in hepatic tissue in the rock bream.